The presence of DNA originating from different individuals in bodily fluids is a well-known biological phenomenon in many clinical and biological scenarios. For example, following bone marrow transplantation, the hemopoietic system of the transplantation recipient will consist of varying proportions of donor's and recipient's cells. The ascertainment of the amount of donor's or recipient's cells has been performed by the detection of genetic differences between the donor and recipient, including gender (Mangioni et al., Bone Marrow Transplant 20:969-73 (1997)) and DNA polymorphisms (Roux et al., Blood 79:2775-83 (1992)). The corollary of this approach is that if the analysed region does not bear a genetic difference between the donor and recipient, then analysis by the current approach will not be possible.
In another example, during pregnancy, detection of fetal DNA in maternal plasma and serum has been previously demonstrated (Lo et al., Lancet 350:9076: 485-7 (1997)). This technology has demonstrated that fetal DNA isolated from maternal plasma and serum can be used for non-invasive prenatal diagnosis (Lo et al., N Eng J Med, 339(24):1734-8 (1998); Faas et al., Lancet 352(9135):1196 (1998); Amicucci et al., Clin Chem 46(2):301 (2000); Chen et al., Prenat Diagn 20(4):355-7 (2000); Saito et al., Lancet 356:1170 (2000)). The clinical application of this phenomenon has been helped by the relatively high absolute and relative concentrations of such circulating fetal DNA in maternal plasma and serum (Lo et al., Am J. Hum Genet 62:768-775 (1998)). Using this approach, noninvasive prenatal detection of a number of conditions has been achieved, including fetal rhesus D status (Lo et al., New Eng J Med 339:1734-1738 (1998)), myotonic dystrophy
(Amicucci et al., Clin Chem 46:301-302 (2000)), achondroplasia (Saito et al., Lancet 356:1170 (2000)) and certain chromosomal translocations (Chen et al., Prenat Diag 20:335-357 (2000); Chen et al., Clin Chem 47:937-939 (2001)). All of these current approaches have utilized the detection of DNA sequences inherited from the father and which are genetically distinguishable from those of the mother (Bianchi, Am J Hum Genet 62(4): 763 (1998). Specifically, the detection of DNA that the fetus has inherited from the mother in maternal plasma or serum has been thought to be impossible. Similar limitations have also been described for the detection of fetal nucleated cells isolated from the cellular fraction of maternal blood (Lo et al., Ann N Y Acad Sci, 731:204 (1994).
Others have detected aberrantly methylated DNA from cancer patients. This has been reported for patients with a variety of cancers, including lung (Esteller, et al., Cancer Res 59(1):67 (1999)) and liver cancer (Wong et al., Cancer Res 59(1):71 (1999)).
Recently, much interest has been focused on the biology of epigenetic phenomena, namely processes which alter the phenotype but which are not associated with changes in DNA sequence (Wolffe, Science 286:481-486 (1999)). One of the best characterised epigenetic processes is DNA methylation (Wolffe et al., Curr Biol. 10:R463-R465 (1999)). A method for discriminating DNA species originating from different individuals in biological fluids using epigenetic, rather than genetic differences between the DNA species would be highly valuable. For example, the epigenetic detection of fetal DNA in a maternal sample would provide a significant advancement enabling additional screening and diagnostic methods.